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Biosimilars of rituximab Posted 27/02/2015

Last update: 20 July 2018

Rituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells. Rituximab destroys B cells and is therefore used to treat diseases that are characterized by excessive number of B cells, overactive B cells or dysfunctional B cells. This includes many lymphomas, leukaemias, transplant rejection and autoimmune disorders.

The originator product, Roche’s MabThera/Rituxan (rituximab), was approved by the US Food and Drug Administration (FDA) in November 1997 and by the European Medicines Agency (EMA) in June 1998 [1]. MabThera/Rituxan had sales of CHF 7.3 billion (Euros 6.4 billion) in 2016, before the advent of biosimilars, see Table 1.

The patents on MabThera/Rituxan expired in the US in September 2016 and in Europe in February 2013 [1]. Some of the rituximab biosimilars and non-originator biologicals* approved or in development are presented in Table 1.

Table 1: Biosimilars and non-originator biologicals* of rituximab approved or in development

Company name, Country

Product name

Stage of development

Amgen, USA

ABP 798

Biosimilar in active development, according to Amgen’s Form 10-K for 2013. One of four biosimilars for oncology indications that Amgen is developing in collaboration with Actavis [2]. Phase III study in NHL expected to be completed in December 2018

Apotex (Apobiologix), Canada

-

In pipeline

AryoGen Pharmed, Iran*

Zytux

Approved by Iran’s FDO in May 2015 [3]

Biocad, Russia*

AcellBia/Usmal

Non-originator biological (AcellBia) approved in Russia in April 2014 [4]. Similar biotherapeutic product (Usmal) approved in Bolivia and Honduras in June 2017 [5]. ‘Similar biologic’ (Acellbia) recommended for approval in India in July 2017 [6]

BioXpress Therapeutics, Switzerland

-

In pipeline [7]

Boehringer Ingelheim, Germany

BI 695500

Phase I and III trials expected to be completed in June and August 2015, respectively, but halted in October 2015 [8]

Celltrion/Hospira (Pfizer), South Korea/USA

Truxima/ Blitzima/ Ritemvia/ Rituzena (previously Tuxella) (CT‑P10)

Phase I trial completed [9]. Phase III trials for RA and lymphoma expected to be completed in January 2017 and February 2017/March 2018, respectively. Collaborating with Teva in Canada and the US [10]. Approved by South Korea's MFDS in November 2016 [11]. Positive phase III trial results reported in December 2016 [12]. Truxima approved by EC in February 2017 [13]. Blitzima, Ritemvia and Rituzena (previously Tuxella) approved by EC in July 2017 [14]. Approved by Australia’s TGA in April 2018 [15]

Celltrion/Teva Pharmaceutical Industries, South Korea/Israel

CT‑P10

Accepted for review by FDA in June 2017 [16]. Rejected by FDA in April 2018 [17]. Resubmitted to FDA in May 2018 [18]

Dr Reddy’s Laboratories, India*

Reditux

Reditux marketed in Bolivia, Chile, India and Peru [19, 20]

Hetero Group, India*

Maball

‘Similar biologic’ approved in India in August 2015 [21]

iBio, USA

-

Rituximab produced in non-transgenic green plants. Alliance made with GE Healthcare in 2012 [22]

Intas Biopharmaceuticals, India*

MabTas

‘Similar biologic’ approved in India in February 2013 [20]

JHL Biotech, Taiwan*

JHL1101 

Phase I PK/PD trial started in February 2016. First patient dosed in a European trail of JHL1101 in March 2017. Made deal with Sanofi giving Sanofi rights to commercialize JHL1101 in China

mAbxience/Laboratorio Elea, Spain/Argentina*

Novex (RTXM83)

Medicamento biológico similar approved in Argentina in October 2013 Phase III trial in Non-Hodgkins Lymphoma expected to be completed in July 2017 [23]

Mabion/Mylan, Poland/India*

MabionCD20

Phase III trial in lymphoma expected to be completed in June 2016 [24]. Agreement signed with Mylan to commercialize MabionCD20 in EU and non-EU Balkan states in November 2016 [25]. Submitted to EMA for approval in June 2018 [26]

Oncobiologics/Viropro, USA

-

Biosimilar in development; one of six monoclonal antibody biosimilars for which the companies are collaborating [27]

Pfizer, USA

PF-05280586

Phase I/II trial in RA completed, extension study and phase III trial in lymphoma expected to be completed in August 2015 and November 2016, respectively

Probiomed, Mexico*

Kikuzubam

Kikuzubam marketed in Mexico [19]. Withdrawn in March 2014

Reliance Life Sciences, India*

RituxiRel

‘Similar biologic’ approved in India in February 2015 [20]

Samsung BioLogics, South Korea

SAIT101

Phase III trial in RA halted in 2012 [28]

Sandoz, Switzerland

Rixathon/ Riximyo (GP2013)

Phase I trial in Japanese NHL patients, phase I/II trial in RA and phase III trial in lymphoma expected to be completed in March 2015, November 2015 and December 2017, respectively. Approved by EC in 19 June 2017 [29]. Approved in Australia in November 2017 [30]. Accepted for review by FDA in September 2017 [31] Rejected by FDA in May 2018 [32]

Shanghai Henlius Biotech, China*

HLX01

Phase III trial started in March 2015

Stada Arzneimittel, Germany

-

Made a deal with Gedeon Richter in 2011 for rituximab [33]

Teva Pharmaceutical Industries/Lonza, Israel/Switzerland

TL011

Phase III trial of TL011 halted in October 2012 [34]. Biosimilars collaboration ended in July 2013 [35]

Torrent Pharmaceuticals/ Reliance Life Sciences, India*

-

Exclusive licensing agreement announced in December 2014 for adalimumab, cetuximab and rituximab ‘similar biologics’ [36]

TRPharma, Turkey*

Redditux

Strategic collaboration agreement made with Dr Reddy’s for three biosimilars in Turkey [37]. Redditux approved in Turkey in January 2018 [38]

Zenotech Laboratories, India*

Rituximab

‘Similar biologic’ approved in India in February 2013 [20]

EC: European Commission; EMA: European Medicines Agency; FDA: US Food and Drug Administration; PK: pharmacokinetics; PD: pharmacodynamics; RA: rheumatoid arthritis; NHL: Non-Hodgkin’s Lymphoma; MFDS: Ministry of Food and Drug Safety; FDO: Food and Drug Organization (Iran’s National Regulatory Authority); TGA: Therapeutic Goods Administration (Australia).
*See editor’s comment 

The fact that the patents on the originator product, Roche’s MabThera/Rituxan (rituximab), already expired in Europe in February 2013, is perhaps spurring development and explains the many companies that are working on biosimilars of rituximab.

Sandoz, the generics division of Novartis, received EC approval for its rituximab biosimilar Rixathon on 19 June 2017 [28]. Both Sandoz and Celltrion have had their rituximab biosimilars accepted for review by FDA [16,29]. However, both Celltrion/Teva and Sandoz, received complete response letters rejecting their rituximab biosimilars in April and May 2018, respectively [17, 30].

Editor’s comment
It should be noted that ‘non-originator biologicals’ approved in Russia, ‘similar biologics’ approved in India, ‘biocomparables’ approved in Mexico, ‘similar biotherapeutic products’ approved in Latin America, ‘biogenerics’ approved in Iran, off-patent biologicals approved in Turkey and ‘medicamento biológico similares’ approved in Argentina might not have been authorized following as strict a regulatory process as is required for approval of biosimilars in the European Union. The EMA (European Medicines Agency) regulatory requirements ensure the same high standards of quality, safety and efficacy for biosimilars as for originator biologicals, and also include a rigorous comparability exercise with the reference product.

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References
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Source: Amgen, Anmat, ClinicalTrials.gov

Comments (1)

Updated info posted 28/02/2015 - by Ak

There is also a Rituximab from Elea Laboratory (from Argentina) called Novex. Elea is part of chemo group from Spain.

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